Antibody response to severe acute respiratory syndrome coronavirus : a Canadian perspective

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Hirose, Krista
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SARS-CoV is the etiological agent of the newly emerged human disease, SARS, and responsible for a global outbreak of atypical pneumonia. As a novel virus, the immunology and characteristics of SARS-CoV infection are not fully understood. To gain insight into the immune response to SARS-CoV infection, the presence and profile of antibodies against SARS-CoV nucleocapsid (N), spike (S), and matrix (M) proteins were evaluated in Canadian probable and suspect cases. From 132 SARS-CoV infected patients, 194 serum samples collected from days 2 to 256 after the onset of illness were analyzed using recombinant SARS-CoV protein-based ELISA and Western blotting. Detection of protein specific antibodies by ELISA revealed that the SARS-CoV N protein elicits the earliest and strongest immune response throughout the course of the disease (97.9Vo), followed by S (73.7Vo),8 (30.9Vo) and M (28.37o) proteins. Further profiling of the IgG, IgA, and IgM antibodies against rhe SARS-Cov N protein demonstrated an IgG-dominated antibody response with respect to the titer and positive rate of detection. Similar results were obtained by Western blotting. Removal of the Cterminal region of SARS-CoV N protein abolished all reactivity with SARS positive patient sera. In contrast, truncating the N-terminal region did not have an adverse effect on detection rates. Collectively, this data suggests that the immunodominant region of SARS-CoV N protein lies within the C-terminus. The present study also assesses the specificity between antibodies to human coronaviruses SARS, OC43, and 2298 in SARS positive, negative and non-SARS sera. Based on recombinant SARS-CoV nucleocapsid protein-based ELISA, immunoblot analysis, and competition assays, antibodies against SARS-CoV and HCoV-2298 crossreact more frequently than antibodies against SARS-CoV and HCoV-OC43. Removal of the N-terminus of SARS-CoV N, containing a highly conserved motif between all HCoVs, reduced the cross-reactivity between anti-HCoV nucleocapsid protein antibodies.